LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia

Francks, C., Maegawa, S., Lauren, J., Abrahams, B. S., Velayos-Baeza, A., Medland, S. E., Colella, S., Groszer, M., McAuley, E. Z., Caffrey, T. M., Timmusk, T., Pruunsild, P., Koppel, I., Lind, P. A., Matsumoto-Itaba, N., Nicod, J., Xiong, L., Joober, R., Enard, W., Krinsky, B., Nanba, E., Richardson, A. J., Riley, B. P., Martin, N. G., Strittmatter, S. M., Moller, H. J., Rujescu, D., St Clair, D., Muglia, P. and Roos, J. L. (2007) LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia. Molecular Psychiatry, 12 12: 1129-1139. doi:10.1038/sj.mp.4002053


Author Francks, C.
Maegawa, S.
Lauren, J.
Abrahams, B. S.
Velayos-Baeza, A.
Medland, S. E.
Colella, S.
Groszer, M.
McAuley, E. Z.
Caffrey, T. M.
Timmusk, T.
Pruunsild, P.
Koppel, I.
Lind, P. A.
Matsumoto-Itaba, N.
Nicod, J.
Xiong, L.
Joober, R.
Enard, W.
Krinsky, B.
Nanba, E.
Richardson, A. J.
Riley, B. P.
Martin, N. G.
Strittmatter, S. M.
Moller, H. J.
Rujescu, D.
St Clair, D.
Muglia, P.
Roos, J. L.
Title LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1359-4184
Publication date 2007-07-31
Year available 2007
Sub-type Article (original research)
DOI 10.1038/sj.mp.4002053
Open Access Status Not yet assessed
Volume 12
Issue 12
Start page 1129
End page 1139
Total pages 11
Editor J. Licinio
Place of publication London, U.K.
Publisher Nature Publishing Group
Language eng
Subject 321011 Medical Genetics
730107 Inherited diseases (incl. gene therapy)
C1
Abstract Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstream of the gene LRRTM1 (Leucine-rich repeat transmembrane neuronal 1) with a quantitative measure of human handedness in a set of dyslexic siblings, when the haplotype was inherited paternally (P=0.00002). While we were unable to find this effect in an epidemiological set of twin-based sibships, we did find that the same haplotype is overtransmitted paternally to individuals with schizophrenia/schizoaffective disorder in a study of 1002 affected families (P=0.0014). We then found direct confirmatory evidence that LRRTM1 is an imprinted gene in humans that shows a variable pattern of maternal downregulation. We also showed that LRRTM1 is expressed during the development of specific forebrain structures, and thus could influence neuronal differentiation and connectivity. This is the first potential genetic influence on human handedness to be identified, and the first putative genetic effect on variability in human brain asymmetry. LRRTM1 is a candidate gene for involvement in several common neurodevelopmental disorders, and may have played a role in human cognitive and behavioral evolution.
Keyword Biochemistry & Molecular Biology
Neurosciences
Psychiatry
Biochemistry & Molecular Biology
Neurosciences & Neurology
Psychiatry
BIOCHEMISTRY & MOLECULAR BIOLOGY
NEUROSCIENCES
PSYCHIATRY, SCI
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID G9826762
R01 MH041953
R01 NS039962
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2008 Higher Education Research Data Collection
School of Medicine Publications
School of Psychology Publications
 
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Created: Mon, 03 Mar 2008, 21:24:17 EST